Mu Xueyan, LeBlanc Gerald A
Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695-7633 USA.
Gen Comp Endocrinol. 2002 Nov;129(2):127-33. doi: 10.1016/s0016-6480(02)00518-x.
Testosterone has been shown to cause developmental arrest of embryonic daphnids (Daphnia magna). The present study was undertaken to determine whether this toxicity might be due to anti-ecdysteroidal activity associated with testosterone. The effect of testosterone on molt frequency of early instar daphnids was first evaluated to determine whether testosterone interfered with this ecdysteroid-regulated process. Molt frequency was delayed by exposure to testosterone and this effect was mitigated by co-exposure to the ecdysteroid 20-hydroxyecdysone. Testosterone exposure concentrations that interfered with molting also elicited developmental abnormalities among neonatal organisms produced by maternal organisms that were continuously exposed to testosterone or among embryos that were removed from unexposed mothers and exposed directly to the hormone. Embryos were significantly protected against the developmental toxicity of testosterone by co-exposure to 20-hydroxyecdysone. Taken together, these results demonstrated that the embryo toxicity of testosterone to daphnids is due largely to its ability to interfere with ecdysteroid control of development. Experiments next were conducted to determine whether testosterone interfered with ecdysteroidal activity by acting as an ecdysone receptor antagonist or by reducing endogenous ecdysone levels. Testosterone significantly antagonized the action of 20-hydroxyecdysone in an ecdysone-responsive cell line. Testosterone had no discernable effect on endogenous ecdysone levels in daphnids. These results demonstrated that (1). ecdysteroids regulate critical processes in daphnid embryo development, (2). testosterone elicits embryo toxicity to daphnids by interfering with ecdysteroid activity, and (3). ecdysteroid receptor antagonism could be one mechanism by which testosterone elicits these effects.
已证明睾酮会导致胚胎水蚤（大型溞）发育停滞。本研究旨在确定这种毒性是否可能归因于与睾酮相关的抗蜕皮甾体活性。首先评估了睾酮对早期龄期水蚤蜕皮频率的影响，以确定睾酮是否干扰了这种由蜕皮甾体调节的过程。暴露于睾酮会延迟蜕皮频率，而同时暴露于蜕皮甾体20 - 羟基蜕皮酮可减轻这种影响。干扰蜕皮的睾酮暴露浓度也会在持续暴露于睾酮的母体产生的新生生物中，或在从未暴露的母体取出并直接暴露于该激素的胚胎中引发发育异常。同时暴露于20 - 羟基蜕皮酮可显著保护胚胎免受睾酮的发育毒性。综上所述，这些结果表明，睾酮对水蚤的胚胎毒性很大程度上是由于其干扰蜕皮甾体对发育控制的能力。接下来进行实验以确定睾酮是通过作为蜕皮酮受体拮抗剂还是通过降低内源性蜕皮酮水平来干扰蜕皮甾体活性。睾酮在蜕皮酮反应性细胞系中显著拮抗20 - 羟基蜕皮酮的作用。睾酮对水蚤内源性蜕皮酮水平没有明显影响。这些结果表明：（1）. 蜕皮甾体调节水蚤胚胎发育中的关键过程；（2）. 睾酮通过干扰蜕皮甾体活性引发对水蚤的胚胎毒性；（3）. 蜕皮甾体受体拮抗作用可能是睾酮引发这些效应的一种机制。
